CENTRE HOSPITALIER RÉGIONAL UNIV;INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE);UNIVERSITÉ DE CAEN NORMANDIE;UNIVERSITÉ DE ROUEN NORMANDIE;CENTRE HOSPITALIER UNIVERSITAIRE DE ROUEN
CD4 T cell help is essential to promote robust cytotoxic T cell responses and could be harnessed to improve outcomes of cancer immunotherapy. To induce CD4+ T cell responses, the inventors have developed artificial antigen presenting cells (AAPCs) that derived from a mouse fibroblast cell line genetically modified to express a single human leukocyte antigen class II molecule (HLA-DR), the human CD80 costimulation as well as CD54 and CD58 adhesion molecules and that constitutively express an antigen (Ag) in peptide or protein forms in different compartments involved in the major histocompatibility complex class II Ag presentation pathway. In particular, the inventors show that the AAPC expressing the Ag peptide in the endoplasmic reticulum (ER) or protein at the plasma membrane were more potent than Epstein-Barr virus (EBV)-transformed B cells to present epitopes to specific CD4+ T- cells. Interestingly, AAPC targeting the Ag peptide in the ER was more efficient than peptide-pulsed AAPC or autologous APC to amplify memory Ag-specific CD4+ T cells that harbor a Th1 profile and express granzyme B. So, the AAPC system is a reliable and standardized tool to generate a high number of Ag-specific CD4+ with effector functions useful for a cancer adoptive immunotherapy. Thus, the present invention relates to an artificial antigen presenting cell that constitutively expresses an antigen along with a HLA-class II molecule and uses thereof in particular for amplifying and/or activating a population of antigen-specific CD4+ T cells.L'aide des lymphocytes T CD4 est essentielle pour favoriser des réponses de lymphocytes T cytotoxiques robustes et pourrait être exploitée pour améliorer les résultats d'une immunothérapie anticancéreuse. Pour induire des réponses de lymphocytes T CD4+, les inventeurs ont développé des cellules présentatrices d'antigène artificiel (AAPC) dérivées d'une lignée de cellules fibroblastiques de souris génétiquement modifiée, pour exprimer une seule molécul
